Scholarly article on topic 'Assessment of human dietary exposure to arsenic through rice'

Assessment of human dietary exposure to arsenic through rice Academic research paper on "Environmental engineering"

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Abstract of research paper on Environmental engineering, author of scientific article — Matthew A. Davis, Antonio J. Signes-Pastor, Maria Argos, Francis Slaughter, Claire Pendergrast, et al.

Abstract Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposurerice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health.

Academic research paper on topic "Assessment of human dietary exposure to arsenic through rice"

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STOTEN-22056; No of Pages 8

Science of the Total Environment xxx (2017) xxx-xxx

Science of the Total Environment

Assessment of human dietary exposure to arsenic through rice

Matthew A. Davis a,b,c, Antonio J. Signes-Pastor a, Maria Argos d, Francis Slaughter a, Claire Pendergrasta, Tracy Punshon a, Anala Gossaia, Habibul Ahsan e, Margaret R. Karagas

a Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, United States b University of Michigan School ofNursing, Ann Arbor, MI, United States c University of Michigan Institute for Social Research, Ann Arbor, MI, United States d University ofIllinois at Chicago School ofPublic Health, Chicago, IL, United States e University ofChicago, Chicago, IL, United States

HIGHLIGHTS

• Rice intake has been associated with increased urinary arsenic concentrations across numerous studies.

• The association between rice intake and human exposure has been demonstrated in populations around the world.

• Maternal rice intake during pregnancy is associated with total arsenic concentrations in infant toenails.

GRAPHICAL ABSTRACT

ARTICLE INFO

ABSTRACT

Article history:

Received 12 August 2016

Received in revised form 14 February 2017

Accepted 14 February 2017

Available online xxxx

Keywords:

Arsenic metabolites

Bio monitoring

Dietary

Exposure

Toenails

Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health.

© 2017 Published by Elsevier B.V.

1. Introduction

* Corresponding author at: Geisel School of Medicine at Dartmouth, Department of Epidemiology, Lebanon, NH 03756, United States.

E-mail address: Margaret.R.Karagas@dartmouth.edu (M.R. Karagas).

Arsenic is a ubiquitous metalloid and its presence in the environment is the result of both natural geologic processes and environmental pollution. Human exposure to arsenic has been associated with a broad

http://dx.doi.org/m1016/j.scitotenv.2017.02.119 0048-9697/© 2017 Published by Elsevier B.V.

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range of adverse effects on health (IARC, 2004; Sharma et al., 2014; UN FAO/WHO, 2011). It is estimated that 140 million people worldwide are exposed to inorganic arsenic (i-As) primarily through the consumption of unregulated contaminated water - the known primary source of i-As human exposure (States et al., 2011). Adverse health effects associated with high levels of i-As exposure are well recognized. However, recent studies have reported an elevated risk of certain cancers, cardiovascular diseases, respiratory conditions, and diabetes associated with relatively low levels of i-As exposure (Amaral et al., 2012; EFSA, 2009; Ettinger et al., 2009; Karagas et al., 2004,2001; Leonardietal.,2012; Navas-Acien et al., 2008; Sohel et al., 2009). Such associations have been observed in populations who were known to consume water with concentrations of i-As well below the World Health Organization's guideline of 10 |ag/L.

While seafood is a major dietary source of exposure due to high levels of arsenobetaine, a non-toxic organic form of arsenic, fruits, fruit juices, and grains are among the primary dietary sources of i-As exposure, especially in regions with access to water low in i-As (Meacher et al., 2002; Taylor et al., 2016; Xue et al., 2010; Yost et al., 2004). Rice, a crop that is grown in flooded plains, is of particular concern as the plant has been shown to bioaccumulate i-As at approximately 10-fold higher rate than other grains such as wheat and barley (Ma et al., 2008; Meharg et al., 2009; Mitani et al., 2009; Williams et al., 2007a, b; Williams et al., 2005). Nevertheless, wide variations exist in the amount and type of arsenic found in rice dependent on both where the plant was grown and the rice species (Bastias et al., 2010; Norton et al., 2012; Signes-Pastor et al., 2016a; Williams et al., 2007a, b; Williams et al., 2005). For instance, rice grown in the U.S. contains higher amounts of total arsenic (t-As) and dimethylarsinic acid (DMA) - the primary arsenic metabolite found in rice (Meharg et al., 2009; Williams et al., 2005). High concentrations of i-As have also been found in rice-based products, including those consumed by infants and young children, who are especially vulnerable to the adverse health effects of i-As exposure (Farzan et al., 2013; Jackson et al., 2012; Signes-Pastor et al., 2016b).

In the context of dietary i-As exposure assessment, it is important to differentiate between estimates of intake of contaminated food versus biological measures of internal dose. Numerous studies have explored the relationship between diet and arsenic biomarker concentrations; however, only a few accounted for arsenic intake from water by direct measurement of water samples (e.g., Gilbert-Diamond et al., 2011). The most common methods to measure dietary intake include the 24hour food recall (administered via an interview or a food diary) and food frequency questionnaires (FFQ). The gold standard of dietary intake assessment is multiple 24-hour food diaries. However, both 24hour food diaries and food frequency questionnaires rely on self-report, and thus are prone to measurement error (Orloff et al., 2009; Tao and Bolger, 1999).

For the present study, we performed a comprehensive literature review of published studies that examined the relationship between rice consumption and arsenic exposure using human biomarkers. Table 1 summarizes the relevant articles included in this review.

2. Biomarkers of human exposure to arsenic

Biomarkers are used to estimate internal dose because they: ( 1 ) represent an aggregate measure that accounts for all routes of exposure and (2) are independent of self-report. Human biological specimens used to estimate internal dose of arsenic exposure include urine, blood, nails, and hair (Marchiset-Ferlay et al., 2012).

Upon ingestion, i-As is rapidly metabolized by the body to monomethylarsonic acid (MMA) and DMA. MMA and DMA are among the end metabolites of the i-As metabolism which may be excreted in the urine unchanged from direct dietary exposure (Vahter, 2002). Urinary arsenic concentration measured in urine spot samples, normalized by creatinine or specific gravity to account for differences in urinary dilution, is a commonly used biomarker of short-term exposure. However,

among individuals with consistent patterns of arsenic exposure urinary arsenic concentration appears to be a reliable source of long-term exposure as well (Kile etal., 2009; Marchiset-Ferlay et al., 2012; Navas-Acien et al., 2009).

The measurement of specific arsenic species in urine is performed by ion exchange high performance liquid chromatography coupled with either inductively coupled plasma mass spectrometry (HPLC-ICP-MS) or hydride generation atomic fluorescence spectrometry (HPLC-HG-AFS). Identification of specific arsenic species in urine is useful to both assess dietary exposure and explore arsenic metabolism (Chowdhury et al., 2003; Concha et al., 1998; Fängström et al., 2009). In addition, arsenic speciation in urine allows the subtraction of species considered relatively non-toxic including arsenobetaine and arsenocholine, predominantly found in seafood products (Navas-Acien et al., 2011). To a lesser extent human blood has been used as a biomarker of short-term arsenic exposure (Hall et al., 2007, 2006).

Human nail (both fingernail and toenail) and hair samples have been extensively used as a biomarker of long-term i-As exposure since unmetabolized i-As tends to be attracted to negative sulfhydryl-groups found in keratin-rich tissues of the integumentary system (Mandal et al., 2003; Slotnick and Nriagu, 2006). The use of hair and nail specimens has the added advantage of being easy to collect (e.g., toenail clippings are of low cost to collect from study participants). However, measurement of t-As in hair and nails (that represents primarily i-As) is potentially less sensitive than arsenic measured in urine. Concentration of tAs in nails and hair tend to provide a better estimate of long-term exposure than arsenic measured in urine due to their growth rate. Nevertheless, considerable care must be taken during nail and hair sample collection and laboratory analysis to avoid external contamination (Mandal et al., 2003). For instance, nails must be thoroughly washed prior to chemical digestion in the laboratory to remove trace contamination of nail polish, dirt or other products.

3. Literature review

3.1. Experimental studies

Epidemiologic evidence points to rice being an independent contributor to dietary i-As exposure. Bioaccessibility of arsenic in rice has been evaluated using in vitro gastro intestinal digestion simulation procedures. These studies have found that between 53% and 102% of t-As in rice is bioavailable (He et al., 2012; Signes-Pastor et al., 2012). One experiment followed two participants who, while consuming < 1 |ag/L arsenic water, were exposed to a wheat-based diet for five days and then switched to a rice-based diet (418 g/day) for another five days (He and Zheng, 2010). The two study participants' urinary t-As concentrations doubled (primarily urinary DMA) upon switching from the wheat-based to the rice-based diet - from a mean of 8.2 |ag of t-As during the wheat-based diet to 16.3 |ag of t-As during the rice-based diet. It was estimated that approximately 63% of the t-As ingested from rice was excreted in the urine. A 7.3-fold increase in urinary t-As concentration (from 6.8 |ag/L to 49.9 |ag/L) that consisted primarily of DMA was reported in a study including six experimental and three control participants after following a five-day rice diet (300 g/day) (Meharg et al., 2014). In this study the five-day rice diet was prepared with rice containing i-As and DMA at a ratio of 1:1 and cooked with deionized water. The authors estimated that 40% of t-As ingested by consuming rice was excreted in the urine. Variation was observed in an individual's concentrations of t-As urine concentrations following a standardized rice portion, as well as urinary t-As excretion over time.

3.2. Child and adult (non-pregnant) populations

In the non-experimental setting, one of the most common used methods to estimate dietary intake is the 24-hour dietary recall. This method includes having a participant recall everything consumed in

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Table 1

Summary of studies that examined associations between rice consumption and human exposure to arsenic.

Order References

Study design Study population

Rice intake assessment Rice

arsenic level

Water arsenic Biomarkers level

Results

He and Zheng, 2010

Experimental Female adults (n = 2).

Meharg et al., 2014

Experimental Male adults (n = 9).

Lovreglio et al., 2012

deCastro et al., 2014

Prospective cohort study

Davis et al., 2012

Kordas et al., 2016

Davis et al., 2014a

Wuetal., 2015

Mass balance of arsenic metabolites. Wheat diet (5 days) vs rice-based diet (418 g of rice/day - 5 days)

Mass balance of arsenic metabolites. 6 participants that followed a rice diet (300 g/day - 5 days) vs 3 participants that did not consume rice (5 days).

Adults Caucasian males Daily food diary starting resident in a coastal area 3 days before the start of

Cross-sectional study

of southern Italy

(n = 12).

Adults, adolescents, and children from NHANES (n = 8300).

the study and continuing throughout the study period.

24-Hour dietary recall including rice, rice cakes/crackers, and rice beverage consumption.

Cross-sectional study

Children from the NHANES (n = 2323).

Cross sectional study

Cross-sectional study

Young children of 5-8 years of age (n = 328) residing in Montevideo, Uruguay.

Adults and children from NHANES (n = 20.497).

48-Hour dietary questionnaire. Rice eater defined as 1/4 cup of cooked rice per day.

Two 24-hour dietary recalls including rice consumption. Children defined as consuming <5 g rice/day vs children >5 g rice/day

48-Hour recall dietary questionnaire including rice consumption.

Cross-sectional study

U.S. adults (n = 6677) belonging to NHANES.

48-Hour recall dietary questionnaire including white and brown rice consumption.

101 |og/kg < 1 |og/kg Mixture of Urinary t-As concentration of i-As, two spot doubled with rice diet in the

25 | g/kg urine two participants (from the

DMA, and samples, the mean value of 8.2 |g to

7.5 |g/kg first in the 16.3 |g). DMA dominated

other morning and urinary arsenic speciation.

arsenic last in the The mean percentage of

species. evening. rice-diet ingested arsenic

excreted in urine was -63%. 99 |g/kg of Distilled Spot urine, Urinary t-As was 7.3-fold i-As, water and 24-hour higher after 4 days consuming

99 |g/kg of urine pass for rice (from 6.8 |g/L to

DMA, and participants 49.9 |g/L). Percentage of

3 |g/kg consuming urinary DMA, and MMA

MMA. rice. increased 65%, and 6%,

respectively after rice consumption. The percentage of urinary i-As decreased - 20% after rice consumption. The percentage of rice ingested arsenic excreted in urine was -40%.

- Refers to Morning spot Rice intake was not shown to

regulation urine samples influence either urinary (<10 |g/kg) for 10 excretion of i-As and its

consecutive methylated species. Rice days. played a minor role in

participants' diet.

- Spot urine Children consumption of rice and adolescents consumption of rice cakes/crackers was related to an increase in urinary DMA (positive regression slopes of 115 and 872, respectively). An increase in urinary MMA was also associated with an increase of rice beverages in adults, and an increase of rice cakes/crackers in children and adolescents (positive regression slopes of 6.4, 65.5, and 103, respectively).

- Spot urine Children "rice eaters" had

I.6-fold higher t-As urinary compared to those non "rice eaters" (from 8.9 | g/L to 5.5 |g/L). An increase of 14.2% of urinary t-As was associated with each 1/4 cup of cooked rice consumption (14.1 g dry weight).

0.45 | g/L Spot urine Sum of urinary arsenic

concentrations (iAs, MMA, and DMA) increased from

II.0 |g/L to 13.5 |g/L with rice consumption > 5 g rice/day.

- Spot urine Association between rice consumption and urinary t-As among both children and adults. An increase of 10 g (dry weight) rice per day was associated with an increase of 9.6% urinary t-As, and an increase of 8.6% in urinary DMA.

- Spot urine Intake of white or brown rice were both associated with -1.6-fold higher urinary sum of arsenic concentrations excluding arsenobetaine

(continued on next page)

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Table 1 (continued)

Order References Study design Study population Rice intake assessment Rice Water arsenic Biomarkers Results

arsenic level level

Gilbert-Diamond etal., 2011

Cross sectional study

Davis et al., 2014b

Cascio et al., 2011

Prospective cohort study

Wei et al., 2014

Melkonian et al., 2013

Park and Lee, 2013

Prospective cohort study

Cross sectional study

Rivera-Nuñez et al., 2012

Pregnant women (n = 229) residing in New Hampshire.

Cross-sectional study

Cross-sectional study

U.S. adults (n = 3027) belonging to the NHANES.

Cross-sectional study

72-Hour recall dietary questionnaire including rice consumption.

Mother-infant pairs (n = 170) residing in New Hampshire, and mother-infant pairs (n = 130) belonging to a validation cohort from Rhode Island.

Adults living in United Kingdom (U.K.) (n = 49).

72-Hour recall dietary questionnaire including rice consumption.

Food frequency questionnaire. Bangladeshi with high consumption of rice (n = 37) vs white Caucasians with lower consumption of rice (n = 12)

Adults living in Araihazar, Bangladesh (n = 18.470, with a subset of 4517 with urinary As metabolites). Korean adults (n = 3404) residing in South Korea belonging to the Korean NHANES.

Adults (n = 343) residing in Michigan belonging to the case-control study of bladder cancer in Michigan.

16 Karagas et al.,

Cross sectional Infants (n = 759)

Food frequency questionnaire including rice consumption. Adults classified as low and high rice consumers (btwice a week vs > twice a week).

Food frequency questionnaire including rice consumption.

Semiquantitative food frequency questionnaire including rice consumption.

Food frequency questionnaire including rice consumption.

Questionnaire and

compared to those who did not consume rice (from 7.9 |g/L to 13.1 |g/L). Among rice eaters, urinary sum of arsenic metabolites excluding arsenobetaine did not differ between participants who primarily consume white rice or brown rice.

Range from Spot urine Urinary t-As was 5.3 |g/L for <0.07 |g/L rice consumers and 3.4 |g/L

to100 | g/L. for non-consumers. Rice

Highly consumers had 0.07 | g/L

right-skewed. higher i-As, 0.18 |g/L higher

MMA, and 1.25 |g/L higher DMA than non-rice consumers. Rice consumption increased urinary loge t-As with a 3 of 0.009 (95% CI: 0.005, 0.013).

- Toenails Toenail t-As concentration from infants exposed to rice consumption during pregnancy was 0.09 | g/g compared to 0.06 |g/g for those non-exposed. An increase of 1/4 cooked rice cups/day during pregnancy was associated with a 16.9% increase in infants toenail t-As concentration.

Refers to Spot urine U.K. Bangladeshi community regulation had 30-fold higher rice

(< 10 |g/kg) consumption than U.K. white

Caucasians. Similar urinary t-As concentrations were found for the Bangladeshi group (28.4 | g/L) and the white Caucasians group (20.6 |g/L). Urinary DMA and i-As concentrations for the U.K. Bangladeshi community was 5- and 2.5-fold higher than for the U.K. white Caucasians.

- Spot urine Participants that consumed rice more than twice a week had 1.1- and 1.2-fold higher urinary t-As (from 2.21 to 2.42 | g/g creatinine) and

DMA (from 1.32 to 1.58 |g/g creatinine) compared to those that consume rice less than twice a week, respectively.

- 50% Spot urine Rice consumption was participants positively associated with with access urinary t-As (Multivariate to well water model 3 = 0.041) (95% CI: <50 |g As/L. 0.032,0.051).

- - Spot urine Rice consumption was

associated with a higher urinary t-As concentration. The adjusted means urinary t-As for low, moderate, and high rice consumption were 99.3,105.4, and 120.1 |g/g creatinine.

- <50 |g/L Spot urine Rice consumption was

positively associated with sum of arsenic concentrations (i-As, MMA, and DMA) with 3 and R2 of 7.51 and 0.008, respectively.

Ranging Mainly Spot urine Urinary t-As was nearly

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Table 1 (continued)

Order References

Study design Study population

Rice intake assessment Rice Water arsenic Biomarkers

arsenic level level

Results

Cleland et al., 2009

Cottingham et al., 2013

Descriptive study

Slotnick et al., 2007

Macintosh et al., 1997

belonging to the NHBCS. diaries including rice and from 4.6 to <10 |g/kg rice-based products. 201 | g i-As/kg.

Korean women adults (n = 108) living in Washington State.

Cross-sectional study

Adults residing in New Hampshire residents (n = 852) belonging to the case-control study of bladder and skin cancer in New Hampshire.

Cross-sectional study

Cross sectional study nested within prospective cohort

Food frequency questionnaire including rice consumption rates, which is an important food item in the Korean community. Annual food frequency questionnaire recording average daily consumption of 120 different diet items.

Adults control participants (n = 440) belonging to the case-control of As in drinking water and bladder cancer in 11 counties o Michigan. Females and males adults (n = 969) belonging to the 19841986 Nurses' Health Study and the Health Professionals Follow-Up Study.

<2 |g/L

<1 |g/Lvs

>1 |g/L

Spot urine and hair

Toenail

Food frequency questionnaire including rice consumption.

Semiquantitative food frequency questionnaire.

Range from <LOD to 99.9 | g/L with a median of 0.38 | g/L.

Toenail

Toenail

double (from 4.97 | g/L to 9.53 | g/L) for infants consuming rice-based products compared to those that did not consume rice. Infant rice cereals and rice-based snacks were positively associated with urinary log10 t-As according to the estimate, 3 = 0.22 (95% CI: 0.11,0.34) and 0.10 (95% CI: 0.04,0.15), respectively. Estimated arsenic exposure from rice was a statistically significant predictor of sum of the urinary arsenic species, but only explained a small percentage of the variability. Toenail t-As increased with household water arsenic concentration. No clear relationship was found between toenail t-As and rice consumption, which may be related to the low rice consumption of the study population (adjusted model 3 for brown rice = 0.23, p-value = 0.29; 3 for white rice = 0.065, p-value = 0.67). Rice consumption was negatively associated with As toenail concentration (3 = -0.137, R2 = 0.017).

Regression coefficient for brown rice consumption per 1 unit increase in daily average servings 0.494 (p-value = 0.0457)

the previous day via either an interview or by a diet diary. The 24-hour dietary recall using an in-person questionnaire interview has been used in the National Health and Nutrition Examination Survey (NHANES). The NHANES is a survey of U.S. non-institutionalized population that also collects objective health measurements designed to make national estimates on diet and health. Several studies have used the NHANES data to examine the association between food intake and urinary arsenic concentrations. These studies reported associations between rice intake and higher t-As exposure in both children and adults (Davis et al., 2012; Davis et al., 2014a; deCastro et al., 2014; Wu et al., 2015). Using NHANES data, rice and rice cakes/crackers intake in g/day was independently associated with an increase of urinary MMA and DMA concentrations among both younger (6-11 years) and older (12-19 years) children (deCastro et al., 2014). In this study, an increase of urinary DMA and MMA (untransformed 3 = 105.6 and 5.6 for DMA and MMA, respectively p-value < 0.15 for both) also was associated with rice beverage consumption in adults between 20 and 84 years old. Using a combination of the NHANES data and the U.S. Department of Agriculture's Food Commodity Intake Database, it was found that children 6-17 years old consuming rice had almost 2-fold higher urinary

t-As - median urinary arsenic concentration of 8.9 |g/L compared to 5.5 |g/L among those non-rice consumers (Davis et al., 2012). Adjusted for other factors, an increase of V cup of cooked rice per day (14.1 g dry weight) was associated with a 14.2% increase in urinary t-As concentration (Davis et al., 2012). In a follow-up study, the same authors found that an increase of 10 g of dry rice per day was associated with an increase of 9.6% urinary t-As, and an increase of 8.6% urinary DMA (Davis et al., 2014a). In both studies the majority of study participants reported to consume water from public sources, which due to regulation is expected to have relatively low i-As concentrations (< 10 |g/L). Another study used NHANES data to examine the association between brown and polished white rice intake separately and urinary arsenic (both t-As and i-As) concentrations in adults (Wu et al., 2015). Both white and brown rice consumption were associated with higher urinary t-As. However, urinary t-As excluding arsenobetaine did not differ between participants who primarily consume white versus brown rice. Mean urinary concentrations of the sum of arsenic metabolites excluding arsenobetaine were 11.5 |g/L among participants who ate < 1 cup/day white rice, 13.1 |g/L among those who ate > 1 cup/day white rice, and 7.9 |g/L among non-rice eaters. For brown rice eaters,

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the mean urinary i-As concentrations were 10.9 |g/L among those who ate < 1 cup/day brown rice only and 13.1 |g/L for those who ate

> 1 cup/day brown rice. The lack of an observed difference between white and brown rice was unexpected. White rice is known to contain less i-As than brown rice as brown rice tends to accumulates arsenic in the outer layers of the pericarp and aleurone, portions of the grain that are removed during the polishing process (Meharg et al., 2008). In the one contrasting study of only 12 adults, whose diets comprised a relatively small proportion of rice, rice intake did not appear to affect either urinary excretion of i-As and its methylated species (Lovreglio etal., 2012).

The FFQ is another common method used to estimate diet in particular long-term dietary patterns (e.g., over the past year). Consequently, among those with variable diets, it may not accurately represent recent, short-term intake - e.g., be reflective of the period of urinary arsenic excretion. The FFQ has been used to examine the association between diet and urinary arsenic concentration among Bangladeshi populations living in the United Kingdom (U.K.) - a group known to consume high amounts of rice (Cascio et al., 2011). Indeed, the Bangladeshi population living in the U.K. had up to 30-fold higher rice consumption compared to Caucasians residing in the U.K. Furthermore, urinary DMA and i-As concentrations were 5- and 2.5-fold higher for the Bangladeshi population (median of 16.9 |g DMA/L and 0.63 |g i-As/L) than for Caucasians (median of 3.16 |g DMA/L and 0.25 |g i-As/L), respectively.

Using NHANES, which also collected FFQ data, another study classified U.S. adults according to their rice frequency consumption as low (<twice a week) and high consumers (>twice a week) (Wei et al., 2014). Those with high rice consumption had higher mean urinary t-As (2.4 |g/g) and DMA (1.6 |g/g) creatinine-adjusted concentrations compared to those with lower rice intake (mean urinary t-As and DMA creatinine-adjusted concentrations of 2.2 and 1.3 |g/g respectively). A similar trend was found in a study population of adults residing in Michigan, U.S. (Rivera-Nunez et al., 2012). While individuals who reported consuming rice in the FFQ were found to have higher urinary t-As concentrations than those who did not report consuming rice, rice explained only a small percentage of the variability in t-As concentrations (Rivera-Nunez et al., 2012). In a large prospective cohort study of adults residing in Araihazar, Bangladesh, spot urine samples were collected along with a 39-item FFQ that inquired about rice consumption (Melkonian et al., 2013). Nearly half of the study population (n = 18.470) was exposed to i-As contaminated drinking water

> 50 |g/L and amount of rice intake was positively associated with urinary t-As concentration (3 = 0.04,95% CI: 0.03, 0.05). A clear correlation between rice consumption estimated by a FFQ and urinary t-As concentrations also has been reported for both the Korean population living in the U.S. and residing in South Korea (Cleland et al., 2009; Park and Lee, 2013).

Toenail t-As concentration, that represents long-term exposure particularly to i-As, has also been related to rice intake. To our knowledge, one of the first research studies on dietary exposure to arsenic used data from the Nurses' Health Study and the Health Professionals Follow-Up Study and reported that consumption of brown rice (estimated using a FFQ) was positively associated with toenail t-As concentration (3 = 0.40, p-value = 0.11) (MacIntosh etal., 1997). A more recent study including participants from a case-control study of bladder and skin cancer in New Hampshire found that toenail t-As concentration increased with household water i-As concentration, but did not identify a relationship between rice consumption and toenail t-As concentration (for brown rice adjusted 3 = 0.23, p-value = 0.29 and white rice 3 = 0.065, p-value = 0.67) (Cottingham et al., 2013). The lack of a relationship in this study may have resulted from the overall low rice consumption of the study population (only 1-3 times per month). Similar results were found in a case-control study carried out in 11 counties of Michigan where rice intake was negatively associated (3 = — 0.137, p-value < 0.05) with toenail t-As concentration (Slotnick et al., 2007). In this study the authors used an FFQ where study participants were

asked on average over the past year how often they consumed foods including soup, rice, and pasta. The authors report the negative association between rice and toenail arsenic may have been due to dietary intake of other foods that confounded the observed relationship.

33. Pregnancy and early childhood

Exposure to arsenic during pregnancy and early childhood is of particular concern due to the vulnerability of the fetus, infants, and young children to environmental contaminants. There is some evidence that exposure i-As early in life may impact growth and health throughout the lifespan (Farzan et al., 2013; IARC, 2004).

It is known that i-As crosses the placental barrier and appears in fetal tissue. Thus maternal exposure during pregnancy is an important area of inquiry. Dietary i-As exposure has been evaluated extensively in the New Hampshire Birth Cohort Study (NHBCS) - an ongoing prospective birth cohort study being conducted in New Hampshire, U.S. where low-level i-As exposure is known to occur (Davis et al., 2014b; Gilbert-Diamond et al., 2011; Karagas et al., 2016). In these studies rice consumption was estimated using a 3-day food diary and spot urinary samples were obtained from women during pregnancy. Mothers who consumed rice had 0.07 |g/L higher urinary i-As, 0.18 |g/L higher urinary MMA, and 1.25 |g/L higher urinary DMA compared to nonrice eaters after adjustment for estimated arsenic intake through the drinking water (Gilbert-Diamond et al., 2011). Among mother-infant pairs it was found that maternal rice intake, also determined with a 3-day food diary, was associated with infants toenail t-As concentration (Davis et al., 2014a, b). Specifically, an increase of 1/4 cup of rice per day was associated with a 16.9% increase in infants toenail t-As concentration indicating that maternal consumption of rice relates fetal exposure, and that infant toenails represent this exposure.

Among one-year old infants participating in the NHBCS, those who were reported to consume rice-based products had mean urinary t-As concentration nearly twice that of those who did not consume rice-based products (5.8 |g/L versus 2.8 |g/L respectively) (Karagas et al., 2016). A similar trend was found among a sample of children between the ages of 5 to 8 years old residing in Montevideo, Uruguay, whose rice intake was estimated using two 24-hour food recall periods (Kordasetal., 2016).

4. Conclusion

Differences in study design, i.e., methods of characterizing both arsenic exposure and rice consumption, geographic and ethnic differences in the study populations, and ages of the study participants all provide challenges to directly compare estimates of the association between rice intake and arsenic exposure. Nevertheless, across diverse populations, studies have consistently found positive associations between rice intake and arsenic exposure. These associations have been reported for infants, adolescents and adults. Most notably, the association between rice intake and arsenic exposure using biomarkers such as urinary arsenic (that represent an estimate of internal dose) has been demonstrated in two experimental studies where participants followed a controlled rice diet. Maternal rice intake during pregnancy also has been associated with infant toenail arsenic concentration at birth, suggesting in utero exposure occurs by rice consumption during pregnancy. Collectively, evidence points to rice being an independent source of arsenic exposure in populations around the world underscoring the importance of strategies to prevent this exposure and understanding its impact on human health.

Funding

The Collaborative on Food with Arsenic and associated Risk and Regulation (C-FARR) is supported by the Dartmouth College Toxic Metals Superfund Research Program (NIH NIEHS P42ES007373) and the

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Children's Environmental Health and Disease Prevention Research Center at Dartmouth (US NIH NIEHS P01ES022832 and EPA RD83459901).

Acknowledgement

This paper, and the four others that accompany it (Punshon et al.; Cubadda et al.; Taylor et al.; Nachman et al.), is a product of the Collaborative on Food with Arsenic and Associated Risk and Regulation (C-FARR), a two year effort led by the Dartmouth Superfund Research Program and Children's Environmental Health and Disease Prevention Research Center. The goal of C-FARR is to synthesize the current information pertaining to arsenic from soil to plate, based on key questions and knowledge gaps identified by policy stakeholders and scientists from interdisciplinary backgrounds, to inform future regulatory and policy decisions affecting dietary arsenic exposure.

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